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Radyoterapi Almış Ratlarda Mezenkimal Kök Hücre Tedavisinin Kolon Anastomozuna Etkileri

Yıl 2026, Cilt: 28 Sayı: 1 , 77 - 83 , 27.04.2026
https://doi.org/10.24938/kutfd.1804010
https://izlik.org/JA95HY44UD

Öz

Amaç: Kolorektal kanserler dünya genelinde en sık görülen üçüncü malignitedir. Rektum kanserinde neoadjuvan radyoterapi (nRT) lokal kontrolü artırmakla birlikte anastomoz kaçağı riskini yükseltmektedir. Mezenkimal kök hücrelerin (MKH) yara iyileşmesini destekleyici etkileri olduğu bilinmektedir. Bu çalışmada, nRT sonrası sıçanlarda kolon anastomoz iyileşmesi üzerine MKH tedavisinin etkilerinin değerlendirilmesi amaçlandı.
Gereç ve Yöntemler: Elli beş Wistar Albino sıçan dört gruba ayrıldı: kontrol, nRT, nRT + lokal MKH ve nRT + lokal + intraperitoneal MKH. nRT gruplarına ameliyat öncesinde tek doz 12 Gy radyoterapi uygulandı. Her bir sıçana anastomoz hattına lokal olarak yaklaşık 1 × 106 adipoz doku kökenli mezenkimal kök hücre 0,1 mL hacimde uygulandı; nRT + lokal MKH grubunda dozun tamamı anastomoz hattına lokal olarak verilirken, nRT + lokal + intraperitoneal MKH grubunda dozun yarısı lokal, kalan yarısı intraperitoneal olarak uygulandı. Anastomoz iyileşmesi barsak patlama basıncı (BPB), histopatolojik ve biyokimyasal incelemelerle değerlendirildi.
Bulgular: Radyoterapi uygulanan gruplarda anlamlı kilo kaybı ve daha düşük BPB değerleri izlendi. Kök hücre uygulanan gruplarda BPB değerleri nRT grubuna kıyasla daha yüksek olmakla birlikte bu fark istatistiksel olarak anlamlı değildi. Histopatolojik ve biyokimyasal parametreler açısından gruplar arasında anlamlı fark saptanmadı. Ancak yalnızca nRT grubunda anastomoz hattında makroskopik ayrışma gözlenirken, kök hücre uygulanan gruplarda makroskopik ayrışma izlenmedi. İmmunfloresan incelemede, anastomoz hattında farklılaşmış kök hücrelerin varlığı gösterildi.
Sonuç: Mezenkimal kök hücre tedavisi, biyokimyasal ve histopatolojik parametrelerde istatistiksel olarak anlamlı bir iyileşme sağlamamakla birlikte, makroskopik anastomoz ayrışmasının görülmemesi ve daha yüksek patlama basıncı eğilimi göstermesi nedeniyle, neoadjuvan radyoterapi sonrası lokal anastomoz iyileşmesini destekleyici potansiyel bir etkiye sahip olabilir. Bu bulgular, mezenkimal kök hücrelerin adjuvan bir tedavi yaklaşımı olarak ileri deneysel ve klinik çalışmalarla değerlendirilmesi gerektiğini düşündürmektedir.

Etik Beyan

Bu çalışma Başkent Üniversitesi Hayvan Deneyleri Etik Kurulu tarafından onaylanmıştır

Destekleyen Kurum

Başkent Üniversitesi Araştırma Fonunca desteklenmiştir.

Proje Numarası

DA 22/01

Kaynakça

  • Frattini M, Balestra D, Suardi S, et al. Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res. 2004;10(12 Pt 1):4015-4021.
  • Yang Q, Qu R, Lu S, Zhang Y, Zhang Z, Fu W. Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite. Int J Med Sci. 2024;21(10):1824-1839.
  • Pommergaard HC, Gessler B, Burcharth J, Angenete E, Haglind E, Rosenberg J. Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis. 2014;16(9):662-671.
  • Wang H, Wei XZ, Fu CG, Zhao RH, Cao FA. Patterns of lymph node metastasis are different in colon and rectal carcinomas. World J Gastroenterol. 2010;16(42):5375-5379.
  • Cammà C, Giunta M, Fiorica F, Pagliaro L, Craxì A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000;284(8):1008-1015.
  • Kruschewski M, Rieger H, Pohlen U, Hotz HG, Buhr HJ. Risk factors for clinical anastomotic leakage and postoperative mortality in elective surgery for rectal cancer. Int J Colorectal Dis. 2007;22(8):919-927.
  • Telem DA, Chin EH, Nguyen SQ, Divino CM. Risk factors for anastomotic leak following colorectal surgery: a case-control study. Arch Surg. 2010;145(4):371-376.
  • Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-646.
  • Marijnen C a. M, Kapiteijn E, van de Velde CJH, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2002;20(3):817-825.
  • Tibbs MK. Wound healing following radiation therapy: a review. Radiother Oncol. 1997;42(2):99-106.
  • Dormand EL, Banwell PE, Goodacre TEE. Radiotherapy and wound healing. Int Wound J. 2005;2(2):112-127.
  • Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-228.
  • Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279-4295.
  • Ceelen W, El Malt M, Cardon A, Berrevoet F, De Neve W, Pattyn P. Influence of preoperative high-dose radiotherapy on postoperative outcome and colonic anastomotic healing: experimental study in the rat. Dis Colon Rectum. 2001;44(5):717-721.
  • Yoo JH, Shin JH, An MS, et al. Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats. J Korean Soc Coloproctol. 2012;28(3):132-139.
  • Gursel MF, Malazgirt Z, Gursel B, Cakir S, Eren Z, Isildak I. Effects of preoperative conventional and hyperfractionated radiotherapy on the healing of rat colonic anastomoses. Onkologie. 2009;32(6):326-330.
  • Yang Y, Wang Q, Luo J, et al. Superoxide Dismutase Mimic, MnTE-2-PyP Enhances Rectal Anastomotic Strength in Rats after Preoperative Chemoradiotherapy. Oxid Med Cell Longev. 2020;2020:3509859.
  • Agren MS, Andersen TL, Mirastschijski U, et al. Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study. Surgery. 2006;140(1):72-82.
  • Waddell A, Ahrens R, Steinbrecher K, et al. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011;186(10):5993-6003.

THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY

Yıl 2026, Cilt: 28 Sayı: 1 , 77 - 83 , 27.04.2026
https://doi.org/10.24938/kutfd.1804010
https://izlik.org/JA95HY44UD

Öz

Objective: Colorectal cancer is the third most common malignancy worldwide. Although neoadjuvant radiotherapy (nRT) improves local control in rectal cancer, it increases the risk of anastomotic leakage. Mesenchymal stem cells (MSCs) have been shown to support wound healing. This study aimed to evaluate the effects of MSC therapy on anastomotic healing after nRT in a rat model.
Material and Methods: Fifty-five Wistar Albino rats were allocated into four groups: control, nRT, nRT + local MSCs, and nRT + local + intraperitoneal MSCs. A single 12 Gy dose of radiotherapy was administered preoperatively to the nRT groups. Each rat received a total of approximately 1 × 10⁶ adipose-derived MSCs in 0.1 mL; in the local MSC group, the entire dose was administered subserosally to the anastomotic site, whereas in the combined group, half of the dose was administered locally and the remaining half intraperitoneally. Anastomotic healing was assessed using burst pressure (BP), histopathological evaluation, and biochemical analyses.
Results: Rats receiving nRT demonstrated significant weight loss and lower BP values. In the MSC-treated groups, BP values were higher compared with the nRT-only group, although these differences did not reach statistical significance. Histopathological and biochemical parameters did not differ significantly among the groups. Notably, gross anastomotic separation was observed only in the nRT-only group, whereas no such separation was detected in the MSC-treated groups. Fluorescent imaging confirmed the presence of differentiated MSCs at the anastomotic site.
Conclusion: Although MSC therapy did not result in statistically significant improvements in biochemical or histopathological parameters, the absence of gross anastomotic separation and the tendency toward higher burst pressure values suggest that MSCs may support local anastomotic healing after neoadjuvant radiotherapy. These findings indicate a potential role for MSC therapy as an adjunctive strategy, warranting further experimental and clinical investigation.

Etik Beyan

This study was approved by Baskent University Ethical Committee for Experimental Resarch on Animals

Destekleyen Kurum

This study supported by Baskent University Research Fund.

Proje Numarası

DA 22/01

Kaynakça

  • Frattini M, Balestra D, Suardi S, et al. Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res. 2004;10(12 Pt 1):4015-4021.
  • Yang Q, Qu R, Lu S, Zhang Y, Zhang Z, Fu W. Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite. Int J Med Sci. 2024;21(10):1824-1839.
  • Pommergaard HC, Gessler B, Burcharth J, Angenete E, Haglind E, Rosenberg J. Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis. 2014;16(9):662-671.
  • Wang H, Wei XZ, Fu CG, Zhao RH, Cao FA. Patterns of lymph node metastasis are different in colon and rectal carcinomas. World J Gastroenterol. 2010;16(42):5375-5379.
  • Cammà C, Giunta M, Fiorica F, Pagliaro L, Craxì A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000;284(8):1008-1015.
  • Kruschewski M, Rieger H, Pohlen U, Hotz HG, Buhr HJ. Risk factors for clinical anastomotic leakage and postoperative mortality in elective surgery for rectal cancer. Int J Colorectal Dis. 2007;22(8):919-927.
  • Telem DA, Chin EH, Nguyen SQ, Divino CM. Risk factors for anastomotic leak following colorectal surgery: a case-control study. Arch Surg. 2010;145(4):371-376.
  • Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-646.
  • Marijnen C a. M, Kapiteijn E, van de Velde CJH, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2002;20(3):817-825.
  • Tibbs MK. Wound healing following radiation therapy: a review. Radiother Oncol. 1997;42(2):99-106.
  • Dormand EL, Banwell PE, Goodacre TEE. Radiotherapy and wound healing. Int Wound J. 2005;2(2):112-127.
  • Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-228.
  • Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279-4295.
  • Ceelen W, El Malt M, Cardon A, Berrevoet F, De Neve W, Pattyn P. Influence of preoperative high-dose radiotherapy on postoperative outcome and colonic anastomotic healing: experimental study in the rat. Dis Colon Rectum. 2001;44(5):717-721.
  • Yoo JH, Shin JH, An MS, et al. Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats. J Korean Soc Coloproctol. 2012;28(3):132-139.
  • Gursel MF, Malazgirt Z, Gursel B, Cakir S, Eren Z, Isildak I. Effects of preoperative conventional and hyperfractionated radiotherapy on the healing of rat colonic anastomoses. Onkologie. 2009;32(6):326-330.
  • Yang Y, Wang Q, Luo J, et al. Superoxide Dismutase Mimic, MnTE-2-PyP Enhances Rectal Anastomotic Strength in Rats after Preoperative Chemoradiotherapy. Oxid Med Cell Longev. 2020;2020:3509859.
  • Agren MS, Andersen TL, Mirastschijski U, et al. Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study. Surgery. 2006;140(1):72-82.
  • Waddell A, Ahrens R, Steinbrecher K, et al. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011;186(10):5993-6003.
Toplam 19 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makalesi
Yazarlar

Kübra Topuk 0000-0002-2244-9875

Adem Şafak 0000-0003-2817-1920

Hüseyin Onur Aydın 0000-0003-3795-5794

Sedat Yıldırım 0000-0002-5735-4315

Çağrı Ahmet Uysal 0000-0001-6236-0050

Pelin Börcek 0000-0001-8565-0667

Caner İncekaş 0000-0001-9019-423X

Meriç Yavuz Çolak 0000-0002-0294-6874

Güler Yavaş 0000-0001-9481-6307

Huriye Eda Özturan Özer 0000-0001-6543-4043

Emine Suna Türkoğlu 0000-0003-4805-1918

Proje Numarası DA 22/01
Gönderilme Tarihi 15 Ekim 2025
Kabul Tarihi 17 Aralık 2025
Yayımlanma Tarihi 27 Nisan 2026
DOI https://doi.org/10.24938/kutfd.1804010
IZ https://izlik.org/JA95HY44UD
Yayımlandığı Sayı Yıl 2026 Cilt: 28 Sayı: 1

Kaynak Göster

APA Topuk, K., Şafak, A., Aydın, H. O., Yıldırım, S., Uysal, Ç. A., Börcek, P., İncekaş, C., Yavuz Çolak, M., Yavaş, G., Özturan Özer, H. E., & Türkoğlu, E. S. (2026). THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY. The Journal of Kırıkkale University Faculty of Medicine, 28(1), 77-83. https://doi.org/10.24938/kutfd.1804010
AMA 1.Topuk K, Şafak A, Aydın HO, vd. THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY. Kırıkkale Üni Tıp Derg. 2026;28(1):77-83. doi:10.24938/kutfd.1804010
Chicago Topuk, Kübra, Adem Şafak, Hüseyin Onur Aydın, vd. 2026. “THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY”. The Journal of Kırıkkale University Faculty of Medicine 28 (1): 77-83. https://doi.org/10.24938/kutfd.1804010.
EndNote Topuk K, Şafak A, Aydın HO, Yıldırım S, Uysal ÇA, Börcek P, İncekaş C, Yavuz Çolak M, Yavaş G, Özturan Özer HE, Türkoğlu ES (01 Nisan 2026) THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY. The Journal of Kırıkkale University Faculty of Medicine 28 1 77–83.
IEEE [1]K. Topuk vd., “THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY”, Kırıkkale Üni Tıp Derg, c. 28, sy 1, ss. 77–83, Nis. 2026, doi: 10.24938/kutfd.1804010.
ISNAD Topuk, Kübra - Şafak, Adem - Aydın, Hüseyin Onur - Yıldırım, Sedat - Uysal, Çağrı Ahmet - Börcek, Pelin - İncekaş, Caner v.dğr. “THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY”. The Journal of Kırıkkale University Faculty of Medicine 28/1 (01 Nisan 2026): 77-83. https://doi.org/10.24938/kutfd.1804010.
JAMA 1.Topuk K, Şafak A, Aydın HO, Yıldırım S, Uysal ÇA, Börcek P, İncekaş C, Yavuz Çolak M, Yavaş G, Özturan Özer HE, Türkoğlu ES. THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY. Kırıkkale Üni Tıp Derg. 2026;28:77–83.
MLA Topuk, Kübra, vd. “THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY”. The Journal of Kırıkkale University Faculty of Medicine, c. 28, sy 1, Nisan 2026, ss. 77-83, doi:10.24938/kutfd.1804010.
Vancouver 1.Kübra Topuk, Adem Şafak, Hüseyin Onur Aydın, Sedat Yıldırım, Çağrı Ahmet Uysal, Pelin Börcek, Caner İncekaş, Meriç Yavuz Çolak, Güler Yavaş, Huriye Eda Özturan Özer, Emine Suna Türkoğlu. THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY. Kırıkkale Üni Tıp Derg. 01 Nisan 2026;28(1):77-83. doi:10.24938/kutfd.1804010

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